Characterizing Mitochondrial Maturation in the Heart

Abstract

Cardiovascular disease is the leading cause of death around the world and the burden is projected to become worse. Because of their ability to supplant the heart’s weak regenerative capabilities, stem cells and their derivatives have been investigated as a potential therapy. However, stem cell-derived cardiomyocytes are less mature than the cells they would be replacing in a clinical setting, causing many functional shortcomings such as unorganized and weak contraction. An in-depth study of how maturation normally occurs is necessary to identify targets to enhance it. As one of the best-known aspects of cardiomyocyte maturation, the mitochondria, and their substrate preferences, dictate the amount of energy a cell produces as well as modulate a cell’s contraction, differentiation, and survival. Similar to the cell itself, the mitochondria mature over time. However, to what extent mitochondrial maturation drives cardiomyocyte maturation is not clear. In this study, we used mass spectrometry to identify the developmental changes across normal cardiac maturation in mitochondria from mice. We detail key shifts in the mitochondrial proteome over time and identify possible regulators of mitochondrial and cardiomyocyte maturation. Pathway and transcription factor analyses highlight transitions over time to more organized, productive mitochondria. Mechanistic evaluation of identified pathways might reveal current bottlenecks for complete maturation of stem cell-derived cardiomyocytes. This work was supported by RMM091621DS008, NIH155993, and NIH160665. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.